From the ACP Diabetes Care Guide

This tool lists what to consider before providing patients with these medications.

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From the ACP Diabetes Care Guide

Use this calculator tool to determine a Glomerular Filtration Rate (GFR).

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From the ACP Diabetes Care Guide

Persons with diabetes are at increased risk for macrovascular disease; microvascular disease, including retinopathy and nephropathy; peripheral and autonomic neuropathies; and lower extremity disease.

• Diabetic retinopathy is the leading cause of noncongenital blindness among adults.
• Diabetes is the most common cause of endstage kidney disease in the United States, especially among Native American, Hispanic, and African American persons. One quarter to one third of patients with type 1 or type 2 diabetes develop some degree of nephropathy.
• Diabetes doubles the risk for cardiovascular disease in men and triples it in women (data from the Multiple Risk Factor Intervention Trial [MRFIT]).
• Patients with diabetes are several-fold more likely to have peripheral arterial disease than patients without diabetes.
• Peripheral arterial disease and foot ulcers in patients with diabetes account for two thirds of all nontraumatic amputations performed in the United States.

Screening for and prevention of these complications are fundamental to the care of patients with diabetes and are important components of quality of care initiatives for diabetes.

NOTE: You may order free copies of the complete ACP Diabetes Care Guide (book and CD-ROM).

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This session answers the following questions:

• In a patient with diabetes and proteinuria of 1 g/d on treatment for hypertension with a BP of 134/80 and proteinuria level 500 mg/d, What should be added, if anything?
• Microalbuminuria is an indicator of CV risk reduction in proteinuria early in the natural history of DM with BP treatment predicts reduced progression of nephropathy

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This session answers the following questions:

• What is the natural history of renal disease in patients with diabetes?
• What is the proper therapy of renal disease in patients with diabetes mellitus?
• Is combination therapy with angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers safe and effective for patients with diabetic renal disease?
• Is there a role of spironolactone in combination therapy with other drugs in patients with diabetic nephropathy?

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• What level of creatinine elevation is "significant" as a cardiovascular risk factor?
• Should coronary artery disease and "traditional" cardiovascular risk factors be treated differently in patients with CKD compared with those without?
• Erythropoietin: Leave management to others?
• Does hypokalemia reduce cardiovascular benefit of hypertension care?
• What else do I do besides treating the blood pressure?

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Transplantation is particularly beneficial in young patients and those with diabetes mellitus (Figure 8). For example, the projected years of life in a patient 20 to 39 years of age on dialysis without diabetes is 31 with a renal transplant and 20 without a transplant. The projected years of life for a patient in the same age group on dialysis who has diabetes is 25 with a transplant and only 8 without a transplant.

Note: Subscription to MKSAP 14 is required to view this material. For more information, visit www.acponline.org.

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Diabetes remains one of the most common causes of renal failure worldwide. Abnormal albumin excretion is an early sign of glomerular disease and may progress slowly from microalbuminuria (30 to 300 mg/d) to macroalbuminuria (more than 300 mg/d) to frank nephrotic syndrome more than 3.5 g/d).

Aggressive blood pressure control, particularly with pharmacologic modulators of the renin-angiotensin-aldosterone axis, such as the ACE inhibitors or angiotensin-II receptor blockers slows this progression.

Glucose control has also been shown to decrease the risk of renal disease in patients with diabetes. Screening for diabetic kidney disease, with annual measurement of microalbumin:creatinine ratios on spot urine samples and serum creatinine concentrations, is recommended. Most authorities also recommend the use of either an ACE inhibitor or ARB in normotensive patients with albuminuria to prevent deterioration of renal status.

Note: Subscription to MKSAP 14 is required to view this material. For more information, visit www.acponline.org.

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Recent progress in preventing and treating end-stage renal disease (ESRD) in the U.S. provides "cautious optimism," but skyrocketing costs are a major concern, said researchers at the U.S. Renal Data System (USRDS).

According to researchers, 104,364 (0.03%) Americans started dialysis or received a kidney transplant in 2004, a nearly 1% decline in renal replacement therapy compared with 2003. The study will appear in the October Journal of the American Society of Nephrology.

The decline in renal replacement therapy came during an increase in type 2 diabetes, a major contributor to kidney disease. The study suggested that improvements in preventive care may be helping to reduce diabetes-related kidney disease, although several years of new data will be needed to confirm this trend.

Also, data from the USRDS show improvement in the quality of dialysis care, including evidence that patients are starting renal replacement therapy at less severe stages of kidney disease. And probabilities of survival for ESRD patients have improved steadily since the late 1980s--especially remarkable since today's dialysis patients are older and sicker than the dialysis population of 20 years ago.

"While most of these findings are grounds for cautious optimism, the same cannot be said for issues of cost," the authors said. Continued growth of the ESRD population caused spending to increase by 57% between 1999 and 2004. Medicare costs for ESRD reached an estimated $20.1 billion, or 6.7% of total Medicare expenditures, while non-Medicare costs rose to $12.4 billion.

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Intensive insulin therapy may have a renoprotective effect in critically ill patients, according to a new study.

Two previously published randomized, controlled trials have indicated that tight glucose control protects the kidneys in critically ill patients. Researchers reanalyzed data from these trials to more closely examine the effect of intensive insulin therapy on renal function. The results appear in the March Journal of the American Society of Nephrology.

The study involved data from 2,707 critically ill medical and surgical patients who did not have end-stage renal disease before hospital admission and were randomly assigned to receive intensive or conventional insulin therapy during hospitalization. Overall, the incidence of acute kidney injury was statistically significantly lower in patients receiving intensive insulin therapy than in those receiving conventional therapy (4.5% vs. 7.6%). A greater renoprotective effect was seen among patients who maintained normal glucose levels.

In surgical patients, oliguria and the need for renal replacement therapy were statistically significantly less common in those receiving intensive insulin therapy compared with conventional therapy (2.6% vs. 5.6% and 4.0% vs. 7.4%, respectively). Medical patients did not derive as much renoprotective benefit from intensive insulin therapy, possibly because patients in this group are usually sicker at hospital admission.

The authors acknowledged several limitations of their study, including examination of a secondary outcome and the limited sample size of some subgroups. However, they concluded that tight glucose control has a renoprotective effect in the critically ill, especially surgical patients.

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Question
In patients with renal disease, do angiotensin-receptor blockers (ARBs) reduce proteinuria more than placebo, other antihypertensive drugs, or their combinations?

Conclusions
In patients with renal disease, ARBs and ACE-Is do not differ for reducing proteinuria. A combination of both drugs is more effective than either drug alone.

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Question
In patients with type 2 diabetes, does pioglitazone reduce cardiovascular events, other adverse events, and mortality or improve health-related quality of life?

Conclusions
Based on 1 randomized trial, pioglitazone does not reduce risk for mortality or cardiovascular events in patients with type 2 diabetes. Some evidence exists that pioglitazone increases risk for such adverse events as weight gain, decrease in hemoglobin level, and edema.

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Question
In patients in the medical intensive care unit (ICU) who were assumed to need intensive care for 3 days, does intensive insulin therapy reduce morbidity and mortality?

Conclusion
In patients in the medical intensive care unit with intended stay for 3 days, intensive insulin therapy reduced morbidity but not mortality.

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Question
Do antihypertensive agents prevent onset of microalbuminuria in patients with diabetes without nephropathy and delay progression in patients with diabetic nephropathy?

Conclusion
Angiotensin-converting enzyme inhibitors delay onset of microalbuminuria in diabetic patients without nephropathy and reduce all-cause mortality in diabetic patients with nephropathy.

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Question
Do angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) have renoprotective effects independent of blood pressure (BP) control?

Conclusion
The renoprotective effects of angiotensin-converting enzymes and angiotensin-receptor blockers independent of their effect on blood pressure control are uncertain.

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Question
In patients with type 1 diabetes diagnosed before 30 years of age, what is the long-term prognosis for developing end-stage renal disease (ESRD) and death? Methods

Conclusions
In patients with type 1 diabetes diagnosed before 30 years of age, risk for end-stage renal disease was 2.2% 20 years after diagnosis. Risk was similar for men and women, and lowest in patients diagnosed before 5 years of age. Risk for death was 6.8% 20 years after diagnosis and was lower in women and in patients diagnosed at a younger age.

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Question
In patients with type 2 diabetes mellitus receiving hemodialysis, does atorvastatin reduce the composite risk for nonfatal myocardial infarction (MI), stroke, and death from cardiac causes?

Conclusion
In patients with type 2 diabetes receiving hemodialysis, atorvastatin did not reduce the composite risk for cardiovascular events or death from cardiac causes more than placebo.

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Question
In patients with hypertension, type 2 diabetes, and normoalbuminuria, do trandolapril and verapamil (used alone or in combination) prevent microalbuminuria?

Conclusion
In patients with hypertension, type 2 diabetes, and normoalbuminuria, trandolapril delayed development of persistent microalbuminuria.

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Question
In patients with type 2 diabetes and microalbuminuria, is a targeted intensive multifactorial intervention more effective than conventional treatment?

Conclusion
In patients with type 2 diabetes and microalbuminuria, a targeted, long-term, intensified, multifactorial intervention using behavioral modification and polypharmacologic therapy was more effective than conventional treatment for reducing cardiovascular and microvascular events.

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Question
In patients with type 2 diabetes mellitus, hypertension, and persistent microalbuminuria, what is the effectiveness of the angiotensin-II–receptor antagonist (ARA) irbesartan for delaying or preventing the development of nephropathy?

Conclusion
In patients with type 2 diabetes mellitus, hypertension, and persistent microalbuminuria, irbesartan delayed progression to nephropathy independent of its effect on blood pressure.

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Question
In patients with type 2 diabetes mellitus, diabetic nephropathy, and hypertension, what effect does the angiotensin-II–receptor antagonist (ARA) irbesartan and the calcium-channel blocker amlodipine have on renal disease?

Conclusion
In patients with type 2 diabetes, nephropathy, and hypertension, irbesartan was more effective in reducing progression of nephropathy independent of the effect on blood pressure than was amlodipine or placebo.

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Question
In patients with type 2 diabetes mellitus and nephropathy, what is the renoprotective effect of the angiotensin-II–receptor antagonist (ARA) losartan?

Conclusions
Losartan was renoprotective in patients with type 2 diabetes mellitus and nephropathy. This effect was beyond that attributable to blood pressure control.

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Question
In patients with type 1 diabetes mellitus and microalbuminuria, what is the effect of angiotensin-converting enzyme (ACE) inhibitors independent of confounding variables?

Conclusions
In patients with type 1 diabetes mellitus and microalbuminuria, angiotensin-converting enzyme inhibitors reduce progression to macroalbuminuria and increase regression to normoalbuminuria. Beneficial treatment effects are greatest for those with the highest levels of baseline microalbuminuria, but no difference exists according to other baseline risk factors. Changes in systemic blood pressure from angiotensin-converting enzyme inhibitors explains some, but not most, of the benefits.

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Background:

Reduction of proteinuria is associated with delayed progression of chronic kidney disease. Reports suggest that angiotensin-receptor blockers (ARBs) reduce proteinuria, but results are variable. The relative effect of ARBs and angiotensin-converting enzyme (ACE) inhibitors, and their combined administration, remains uncertain.

Purpose:

To establish the effect of ARBs versus placebo and alternative treatments, and the effect of combined treatment with ARBs and ACE inhibitors, on proteinuria.

Data Sources:

English-language studies in MEDLINE and the Cochrane Library Central Register of Controlled Trials (January 1990 to September 2006), reference lists, and expert contacts.

Study Selection:

Randomized trials of ARBs versus placebo, ACE inhibitors, calcium-channel blockers, or the combination of ARBs and ACE inhibitors in patients with or without diabetes and with microalbuminuria or proteinuria for whom data were available on urinary protein excretion at baseline and at 1 to 12 months.

Data Extraction:

Two investigators independently searched and abstracted studies.

Data Synthesis:

Forty-nine studies involving 6181 participants reported results of 72 comparisons with 1 to 4 months of follow-up and 38 comparisons with 5 to 12 months of follow-up. The ARBs reduced proteinuria compared with placebo or calcium-channel blockers over 1 to 4 months (ratio of means, 0.57 [95% CI, 0.47 to 0.68] and 0.69 [CI, 0.62 to 0.77], respectively) and 5 to 12 months (ratio of means, 0.66 [CI, 0.63 to 0.69] and 0.62 [CI, 0.55 to 0.70], respectively). The ARBs and ACE inhibitors reduced proteinuria to a similar degree. The combination of ARBs and ACE inhibitors further reduced proteinuria more than either agent alone: The ratio of means for combination therapy versus ARBs was 0.76 (CI, 0.68 to 0.85) over 1 to 4 months and 0.75 (CI, 0.61 to 0.92) over 5 to 12 months; for combination therapy versus ACE inhibitors, the ratio of means was 0.78 (CI, 0.72 to 0.84) over 1 to 4 months and 0.82 (CI, 0.67 to 1.01) over 5 to 12 months. The antiproteinuric effect was consistent across subgroups.

Limitations:

Most studies were small, varied in quality, and did not provide reliable data on adverse drug reactions. Proteinuria reduction is only a surrogate for important progression of renal failure.

Conclusion:

The ARBs reduce proteinuria, independent of the degree of proteinuria and of underlying disease. The magnitude of effect is similar regardless of whether the comparator is placebo or calcium-channel blocker. Reduction in proteinuria from ARBs and ACE inhibitors is similar, but their combination is more effective than either drug alone. Uncertainty concerning adverse effects and outcomes that are important to patients limits applicability of findings to clinical practice.

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